title: MITOPLD is a mitochondrial protein essential for nuage formation and piRNA biogenesis in the mouse germline.
abstract: MITOPLD is a member of the phospholipase D superfamily proteins conserved among diverse species. Zucchini (Zuc), the Drosophila homolog of MITOPLD, has been implicated in primary biogenesis of Piwi-interacting RNAs (piRNAs). By contrast, MITOPLD has been shown to hydrolyze cardiolipin in the outer membrane of mitochondria to generate phosphatidic acid, which is a signaling molecule. To assess whether the mammalian MITOPLD is involved in piRNA biogenesis, we generated Mitopld mutant mice. The mice display meiotic arrest during spermatogenesis, demethylation and derepression of retrotransposons, and defects in primary piRNA biogenesis. Furthermore, in mutant germ cells, mitochondria and the components of the nuage, a perinuclear structure involved in piRNA biogenesis/function, are mislocalized to regions around the centrosome, suggesting that MITOPLD may be involved in microtubule-dependent localization of mitochondria and these proteins. Our results indicate a conserved role for MITOPLD/Zuc in the piRNA pathway and link mitochondrial membrane metabolism/signaling to small RNA biogenesis.
authors.affiliation: Division of Human Genetics, Department of Integrated Genetics, National Institute of Genetics, Research Organization of Information and Systems, Mishima, Shizuoka, 411-8540, Japan. toshiaki.watanabe@yale.edu
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Watanabe
authors.forename: Shinichiro
authors.initials: S
authors.lastname: Chuma
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Yamamoto
authors.forename: Satomi
authors.initials: S
authors.lastname: Kuramochi-Miyagawa
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Totoki
authors.forename: Atsushi
authors.initials: A
authors.lastname: Toyoda
authors.forename: Yuko
authors.initials: Y
authors.lastname: Hoki
authors.forename: Asao
authors.initials: A
authors.lastname: Fujiyama
authors.forename: Tatsuhiro
authors.initials: T
authors.lastname: Shibata
authors.forename: Takashi
authors.initials: T
authors.lastname: Sado
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Noce
authors.forename: Toru
authors.initials: T
authors.lastname: Nakano
authors.forename: Norio
authors.initials: N
authors.lastname: Nakatsuji
authors.forename: Haifan
authors.initials: H
authors.lastname: Lin
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Sasaki
mesh_terms: D000818:Animals; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism; D004722:Endoribonucleases / Q000235:genetics / Q000378:metabolism; D005854:Germ Cells / Q000166:cytology / Q000502:physiology; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D008297:Male; D008540:Meiosis / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D024101:Mitochondrial Proteins / Q000235:genetics / Q000378:metabolism*; D010739:Phospholipase D / Q000235:genetics / Q000378:metabolism*; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism*; D018626:Retroelements; D015398:Signal Transduction / Q000502:physiology; D013091:Spermatogenesis / Q000502:physiology*; D013737:Testis / Q000166:cytology
chemical_list: D029721:Drosophila Proteins; D007527:Isoenzymes; D024101:Mitochondrial Proteins; D034741:RNA, Small Interfering; D018626:Retroelements; D004722:Endoribonucleases; C521347:Zuc protein, Drosophila; D010739:Phospholipase D; C558126:mitoPLD protein, mouse